Flexible bag

ABSTRACT

A flexible bioprocess bag comprising a number of flexible panels which are sealed to each other such that when the bag is filled they form at least a bottom of the bag and a side surface of the bag, wherein one of the flexible panels is called a bottom panel and when the bag is filled said bottom panel will constitute the bottom of the bag and parts of the side surface of the bag, said parts of the side surface being bent side parts of the bottom panel.

CROSS-REFERENCE TO RELATED APPLICATION

The present patent application is a continuation of U.S. patentapplication Ser. No. 16/757,579, filed Apr. 20, 2020, which is aNational Stage application, filed under 35 U.S.C. § 371, of theInternational Patent Application No. PCT/EP2018/079298 filed on Oct. 25,2018, which claims priority to U.S. Provisional Patent Application No.62/579,195, filed Oct. 31, 2017, all of which are hereby incorporated byreference in their entireties.

TECHNICAL FIELD OF THE INVENTION

The present invention relates to a flexible bioprocess bag comprising anumber of flexible panels. In particular, it relates to large scaleflexible bioprocess bags for use as single use liners in cylindricalbioreactor or mixer vessels. It also relates to a cylindrical bioreactoror mixer, a method of loading a flexible bioprocess bag in a cylindricalbioreactor or mixer and a method of cultivating cells in a cylindricalbioreactor vessel.

RELATED ART

Flexible bags for holding and possibly handling fluids can be providedin different ways. Flexible panels may be sealed to each other to makeup a bag of a suitable form. In for example a bioreactor a cylindricalvessel is often used and a flexible bag is provided inside the vessel asa disposable liner. If a liner which is not matching the form of thevessel in a good way is provided into the vessel there may be wrinklesin the liner or areas of stress concentration from the fluid headpressure pushing on the film in an unsupported region. Wrinkles maycause problems with fluid getting stacked in the wrinkles. Furthermore,in for example bioreactors a close fit between the form of the vesseland the liner is suitable for improving heat transfer.

SUMMARY

An object of the invention is to provide an improved flexible bioprocessbag.

A further object of the invention is to provide a flexible bag fittingclose inside a cylindrical vessel that minimizes film folds.

This is achieved in a flexible bag according to claim 1.

According to one aspect of the invention a flexible bioprocess bag isprovided comprising a number of flexible panels which are sealed to eachother such that when the bag is filled they form at least a bottom ofthe bag and a side surface of the bag, wherein one of the flexiblepanels is called a bottom panel and when the bag is filled said bottompanel will constitute the bottom of the bag and parts of the sidesurface of the bag, said parts of the side surface being bent side partsof the bottom panel.

Hereby a flexible bioprocess bag is achieved with an improved designwhich provides a robust bag with suitable geometry. The flexible bagaccording to the invention is suitable for use inside a cylindricalvessel. Wrinkles and film folds are minimized when the flexible bag isprovided inside a cylindrical vessel and hereby stagnant fluid zones canbe eliminated or decreased. In such stagnant fluid zones suspendedsolids can accumulate in for example a mixing bag or a bioreactor. Thiscan thus be avoided by the present invention. Furthermore, with theflexible bag according to the invention it can be ensured that the filmlayer is kept thin between the process fluid and a vessel surfacewithout pockets of entrapped air that can form from film folds. This issuitable for improving heat transfer. Furthermore, with a flexible bagaccording to the invention fluid hold up in the bag during draining canbe reduced.

According to another aspect of the invention a cylindrical bioreactor ormixer comprising the flexible bioprocess bag according to the inventionis provided.

According to another aspect of the invention a method of loading aflexible bioprocess bag in a cylindrical bioreactor or mixer isprovided. The method comprises the steps of:

-   -   providing a cylindrical bioreactor or mixer vessel;    -   providing the flexible bioprocess bag as described above;    -   loading said flexible bioprocess bag in said cylindrical        bioreactor or mixer vessel.

According to another aspect of the invention a method of cultivatingcells in a cylindrical bioreactor vessel is provided. Said methodcomprises the steps of:

-   -   loading a flexible bioprocess bag in a cylindrical bioreactor        vessel according to the method as described above;    -   providing a cell culture medium to an inner volume of said        flexible bioprocess bag;    -   providing cells to the inner volume of said flexible bioprocess        bag;    -   cultivating the cells in the inner volume under agitation.

In one embodiment of the invention said bent side parts of the bottompanel are two essentially triangular parts of the side surface of thebag.

In one embodiment of the invention the bottom panel is an elongatedpanel comprising a middle part having two opposite first side edges,said elongated panel further comprising two essentially triangular partsconnected one to each of the first side edges of the middle part. Thetwo essentially triangular parts may each have a base integral with themiddle part and two edges converging towards a top.

In one embodiment of the invention said middle part is essentially aquadrilateral with side edges of substantially the same length as adiameter of a cylinder substantially matching the form of the sidesurface of the bag when the bag is filled, wherein said essentiallytriangular parts are connected along its bases one to each of said firstside edges of the middle part with the tops of the triangular partspointing away from each other.

In one embodiment of the invention the two first side edges of themiddle part where the bases of the essentially triangular parts areconnected are shorter than two remaining side edges, called second sideedges of the middle part and the two second side edges are curved suchthat a circle having the same diameter as a cylinder substantiallymatching the form of the side surface of the bag when the bag is filledstill fits inside the middle part.

In one embodiment of the invention an angle of a top of the essentiallytriangular parts is within the range of 75-105 degrees. In oneembodiment of the invention an angle of a top of the essentiallytriangular parts is within the range of 85-95 degrees.

In one embodiment of the invention the flexible panels of the bagcomprise the bottom panel and furthermore two side panels eachcomprising two side edges which side panels are sealed to each otheralong its side edges and sealed to the bottom panel to form anessentially cylindrical side surface together with the essentiallytriangular parts of the bottom panel.

In one embodiment of the invention the flexible panels of the bagcomprise the bottom panel and furthermore one single side panel havingtwo side edges which are sealed to each other and said single side panelis also sealed to the bottom panel to form an essentially cylindricalside surface together with the essentially triangular parts of thebottom panel.

In one embodiment of the invention the flexible panels of the bagfurther comprise a top panel essentially of the same form as the bottompanel and one or more side panels, said flexible panels being sealed toeach other such that a closed bag of essentially cylindrical form isachieved when the bag is filled.

In one embodiment of the invention at least one connector is provided toany one of the flexible panels for the purpose of exchanging fluid froman external space to an internal space of the bag.

In one embodiment of the invention at least one impeller is provided toany one of the flexible panels for the purpose of mixing content insidethe bag.

In one embodiment of the invention at least one sensor is provided toany one of the flexible panels for the purpose of measuring one or morephysical or chemical attributes of the content in the bag.

In one embodiment of the invention said flexible bag is a liner for acylindrical bioreactor vessel or mixer.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 a is a schematic front view of a filled flexible bag according toone embodiment of the invention.

FIG. 1 b is a schematic side view of the same filled flexible bag asshown in FIG. 1 a.

FIG. 1 c is a schematic perspective view of the flexible bag as shown inFIGS. 1 a and 1 b.

FIG. 1 d is a schematic perspective view from the bottom of the flexiblebag as shown in FIGS. 1 a, b and c.

FIG. 2 shows schematically a bottom panel of a flexible bag according toone embodiment of the invention.

FIG. 3 a is a schematic view of a bottom panel of a flexible bagaccording to one embodiment of the invention.

FIG. 3 b is a schematic view of a top panel of a flexible bag accordingto one embodiment of the invention.

FIG. 4 a is a schematic view of a first side panel of a flexible bagaccording to one embodiment of the invention.

FIG. 4 b is a schematic view of a second side panel of a flexible bagaccording to one embodiment of the invention.

FIG. 5 is a schematic view of flexible panels of a flexible bag beforesealing of the panels to form a bag according to one embodiment of theinvention.

FIG. 6 is a schematic view of a single side panel of a flexible bagaccording to another embodiment of the invention.

DETAILED DESCRIPTION OF EMBODIMENTS

A flexible bag is provided comprising a number of flexible panels whichare sealed to each other such that when the bag is filled they form atleast a bottom of the bag and a side surface of the bag. According tothe invention one of the flexible panels is called a bottom panel andwhen the bag is filled said bottom panel will constitute the bottom ofthe bag and parts of the side surface of the bag. Said parts of the sidesurface of the bag being bent side parts of the bottom panel. In someembodiments of the invention said bent side parts of the bottom panelare two essentially triangular parts. Essentially triangular would inthis patent application include a triangle but also include a trianglehaving somewhat curved sides instead of straight sides, i.e. anessentially triangular part comprises one base and two sides convergingto meet each other, where both the base and the sides can be somewhatcurved or straight. The bent side parts can in another embodiment of theinvention be quadrilateral instead of triangular.

FIG. 1 a is a schematic front view of a filled flexible bag 1 accordingto one embodiment of the invention and FIG. 1 b is a schematic side viewof the same filled flexible bag as shown in FIG. 1 a . FIG. 1 c is aschematic perspective view of the same flexible bag as shown in FIGS. 1a and 1 b . FIG. 1 d is a schematic perspective view from the bottom ofthe same flexible bag as shown in FIGS. 1 a, b and c.

The flexible bag 1 according to this embodiment of the inventioncomprises four flexible panels 3 a, 3 b, 4 a, 4 b which are sealed toeach other such that when the bag is filled they form a bottom 7 of thebag, a top 9 of the bag and a side surface 11 of the bag. One of theflexible panels is called a bottom panel 3 a and when the bag is filledsaid bottom panel 3 a will constitute both the bottom 7 of the bag andparts of the side surface 11. Said parts of the side surface 11 are bentside parts 10 a, 10 b of the bottom panel 3 a. Two bent side parts 10 a,10 b of the bottom panel 3 a are in this embodiment essentiallytriangular and are also called essentially triangular parts 10 a, 10 b.These bent side parts, also called triangular parts 10 a, 10 b can bebetter seen in FIG. 2 . The bent side parts 10 a, 10 b will be bent fromthe bottom 7 to form parts of the side surface 11. In this embodimentthe bent side parts 10 a, 10 b are essentially triangular in formhowever in other embodiments of the invention the bent side parts 10 a,10 b can have other geometries, such as quadrilateral. In the embodimentof the invention as shown in FIGS. 1 a-1 d there is also a top panel 3 bhaving the same geometry and dimensions as the bottom panel 3 a. Inanother embodiment of the invention a top 9 of the bag can be designeddifferently. For example, the side panels 4 a, 4 b can be sealedtogether to provide a closure at the top of the bag. Geometry of abottom panel 3 a and possibly also a top panel 3 b according to someembodiments of the invention is discussed in further detail in relationto FIG. 2 . FIG. 3 a shows one example of a bottom panel 3 a which canbe used in a flexible bag according to one embodiment of the inventionand FIG. 3 b shows one example of a top panel 3 b which can be used in aflexible bag according to one embodiment of the invention.

The flexible bag 1 according to this embodiment comprises further twoside panels 4 a, 4 b. Said two side panels 4 a, 4 b are identical inform and dimensions and comprises each two side edges 14 a, 15 a, 14 b,15 b, see FIGS. 4 a and 4 b . Each side edge of said side panels issealed to one of the side edges of the other side panel such that anenclosing side surface 11 of the bag is achieved. Furthermore, the sidepanels 4 a, 4 b are sealed to the bottom panel 3 a to form anessentially cylindrical side surface 11 together with the essentiallytriangular parts 10 a, 10 b of the bottom panel 3 a. In FIGS. 4 a and 4b two examples of side panels 4 a, 4 b according to one embodiment ofthe invention is shown. In another embodiment of the invention only onesingle side panel 4 is provided, see FIG. 6 . In that embodiment of theinvention the single side panel 4 is wrapped around the circumference ofthe bag and the side edges of the single side panel 4 are sealed to eachother. The single side panel 4 is furthermore sealed to the bottom panelsuch that an essentially cylindrical side surface is formed togetherwith the essentially triangular parts 10 a, 10 b of the bottom panel 3a. In still another embodiment of the invention more than two sidepanels are provided. Any number of side panels could be provided. Saidside panels are sealed to make up an overall geometry essentially as theone shown in FIG. 6 .

The flexible bag 1 of FIGS. 1 a-1 d can be folded when empty. This issuitable for transport and/or storage. The design of the flexible panelsallows it to be folded flat when empty. The convergence of the sidepanels and the top or bottom panels into a triangular point provides anatural fold line in three locations (horizontally alongside panel 4 aor 4 b from triangular point to point and along the horizontal centralaxis of top or bottom panel 3 a or 3 b), so that the top and bottompanel can be folded flat either over or under the side surface. This isespecially advantageous when rigid ports and tubing are attached to thefilm panel restricting its ability to easily fold in certain directions.All seams can be joined together through the process of heat sealing ina reliable and easy manner when the bag of this panel construction iscompressed in the flat state enabling robust manufacturing of the bag.

FIG. 2 shows schematically the design of a bottom panel 3 a according toone embodiment of the invention. As discussed above the design of a toppanel 3 b can be identical however in the text describing FIG. 2 it isreferred to a bottom panel 3 a. The bottom panel 3 a is an elongatedpanel comprising a middle part 21 and two essentially triangular parts10 a, 10 b. The middle part 21 comprises two opposite first side edges23 a, 23 b and the triangular parts 10 a, 10 b are connected one to eachof said first side edges 23 a, 23 b of the middle part 21. Said middlepart 21 is essentially a quadrilateral with four side edges. Two of theside edges are the two first side edges 23 a, 23 b mentioned above andthe two remaining side edges are called second side edges 24 a, 24 b andare also positioned opposite each other. The first and second side edges23 a, 23 b, 24 a, 24 b are all of substantially the same length as adiameter d of a cylinder substantially matching the form of the sidesurface 11 of the bag when the bag is filled. Said essentiallytriangular parts 10 a, 10 b are connected along its bases 110 a, 110 bone to each of the two first side edges 23 a, 23 b of the middle partwith a top 111 a, 111 b of the triangular parts 10 a, 10 b pointing awayfrom each other.

In this embodiment of the invention the two first side edges 23 a, 23 bof the middle part 21 where the bases 110 a, 110 b of the essentiallytriangular parts 10 a, 10 b are connected are shorter than the twosecond side edges 24 a, 24 b of the middle part 21 and the two secondside edges 24 a, 24 b are curved such that a circle c having the samediameter d as a cylinder substantially matching the form of the sidesurface 11 of the bag 1 when the bag is filled still fits inside themiddle part 21. Since the cylinder of diameter d fits inside the middlepart 21, the triangular parts 10 a and 10 b when extending up in theinflated portion do not have to support the force exerted by the fluidhead pressure while unsupported by the tank. This prevents excessivestress at the tri-seam area by having the triangular parts 10 a and 10 balways in contact with the vessel surface. Any gaps between the film andthe vessel, especially in this location, can cause the fluid headpressure to exert a force against the triangular part which pulls downone panel of the tri-seam and can cause leaks. In this way, the panelgeometry optimizes the amount of surface to surface contact between thefilm and the vessel support structure without the use of excess filmthat can lead to wrinkles.

The angle α of the tops 111 a, 111 b of the two essentially triangularparts 10 a, 10 b is within the range of 75-105 degrees. In oneembodiment of the invention the angle α is within the range of 85-95degrees and in one embodiment of the invention the angle α is 90degrees.

This design of a bottom panel 3 a of the flexible bag 1 according to theinvention will provide a flexible bag which can be provided as a linerinside a cylindrical vessel, for example a bioreactor, with someimportant advantages. One advantage with this design of a flexible bagis that wrinkles can be avoided in the part of the flexible bag wherethe bottom 7 of the bag meets the side surface 11 of the bag. Thetriangular parts 10 a, 10 b of the bottom panel 3 a which will be foldedup from the bottom to constitute parts of the side surface 11 of the bagcontributes to decreased risk of wrinkles. The design can alsoaccommodate protrusions such as baffles (used to enhance bioreactormixing performance) which increases the circumference of the tank for afixed tank diameter. The circumference of the bag is increased byincreasing the panel width while decreasing extra film that would resultin wrinkles through the curvature formed by the arcs 24 a and 24 b(curved form of second side edges 24 a, 24 b) in FIG. 2 . Furthermore,the angle of the tops of the triangular parts 10 a, 10 b being in oneembodiment essentially 90 degrees or within the range of 75-105 degreeswill facilitate a vertical orientation of the bag when it is filledsince the straight side panel seams when joined together will not causethe top or bottom panel to buckle when inserted into a cylinder with avertical side wall at 90 degrees to its bottom surface.

In some embodiments of the invention one or more connectors can beprovided to any one of the flexible panels 3 a, 3 b, 4 a, 4 b for thepurpose of exchanging fluid from an external space to an internal spaceof the bag 1. Furthermore, one or more impellers can be provided to anyone of the flexible panels 3 a, 3 b, 4 a, 4 b for the purpose of mixingcontent inside the bag 1. Furthermore, one or more sensors can beprovided to any one of the flexible panels 3 a, 3 b, 4 a, 4 b for thepurpose of measuring one or more physical or chemical attribute of thecontent in the bag 1.

FIGS. 3 a, 3 b, 4 a and 4 b show schematically the flexible panels of aflexible bag according to one embodiment of the invention. FIG. 3 ashows a bottom panel 3 a, FIG. 3 b shows a top panel 3 b, FIG. 4 a showsa first side panel 4 a and FIG. 4 b shows a second side panel 4 b. Inthis embodiment of the invention the bottom panel 3 a comprises animpeller 33 and a connector and/or sensor 35. The top panel 3 bcomprises 9 different connectors and/or sensors 37 a-i and the firstside panel 4 a comprises 11 different connectors and/or sensors 39 a-k.The number of connectors/sensors can of course be varied.Connector/sensors can as well be provided to the second side panel 4 b.

The first and second side panels 4 a, 4 b comprises as described aboveeach two opposite side edges 14 a, 15 a, 14 b, 15 b which each is sealedto one side edge of the other side panel to form an enclosing sidesurface 11 of the flexible bag 1. The two remaining edges of each of theside panels 4 a, 4 b are called bottom panel sealing edge 16 a, 16 b andtop panel sealing edge 17 a, 17 b. The bottom panel sealing edges 16 a,16 b and the top panel sealing edges 17 a, 17 b are formed to match thedesign of the bottom panel 3 a and the top panel 3 b when the triangularparts 10 a, 10 b are folded up constituting parts of the side surface 11of the flexible bag 1.

FIG. 5 shows one embodiment of the invention where the flexible panels 3a, 3 b, 4 a, 4 b are cut out from one single piece of flexible sheet andin this embodiment, the number of seals required to form thethree-dimensional bag is reduced because the panels are joined at theadjacent tangent edges of the joining arc segments. Misalignment duringfabrication of the panels is reduced because there is just one sheet offilm that is folded and sealed at the edges.

FIG. 6 is a schematic view of a single side panel 4 of a flexible bagaccording to another embodiment of the invention. In this embodiment ofthe invention one single side panel 4 is provided instead of two sidepanels 4 a, 4 b as shown in FIGS. 4 a and 4 b.

In one embodiment of the invention the internal volume of the flexiblebag when filled is at least 10 L, such as at least 50 L. The internalvolume can be up to 1 m3 or even 2 m3, with the advantages of reducedfold/wrinkle formation and reduced stress concentration beingparticularly pronounced for larger bags, e.g. in the 50 L to 2 m3interval. In one embodiment of the invention the flexible bag ispresterilized, e.g. by gamma irradiation.

The flexible bag according to the invention can be provided as a linerfor a cylindrical vessel, for example a bioreactor vessel. Thedimensions of such a liner should be adapted to the dimensions of thevessel and specifically the circumference of the essentially cylindricalside surface of the bag should closely match the circumference of thevessel including any number of protruding internal surfaces in thevessel, for example baffles. In one example, baffles can take the shapeof a triangular protrusion with one side joined at the vessel side walland extending into the inner region of the vessel between 1/10 and 1/12of the tank diameter. These baffles are commonly used to improve themixing performance in cylindrical tanks.

It may be important to provide a liner (flexible bag) which will stay asclose as possible to an inner wall of a vessel. This can be importantfor heat transferring and for supporting of the flexible bag andavoidance of tension to the seals of the flexible bag. Furthermore, asdescribed above wrinkles in the flexible bag should be avoided. Theflexible bag according to the invention is suitable regarding all theseaspects. An essentially cylindrical flexible bag is provided accordingto the invention which can stay close to the inner walls of acylindrical vessel and which reduces risk of wrinkles especially where abottom of the flexible bag turns into a side surface.

A cylindrical bioreactor or mixer comprising the flexible bioprocess bagaccording to the invention is also provided. Such a cylindricalbioreactor or mixer can have a flat bottom or a bottom being somewhatelliptical or conical. The bottom may e.g. have a frustoconical orspherical cap shape, optionally with one or more openings for attachmentof an impeller drive, drainage tubing and/or supply lines for gases orliquids.

Furthermore, a method of loading a flexible bioprocess bag in acylindrical bioreactor or mixer is provided. The method comprises thesteps of:

-   -   providing a cylindrical bioreactor or mixer vessel;    -   providing the flexible bioprocess bag as described above;    -   loading said flexible bioprocess bag in said cylindrical        bioreactor or mixer vessel.

Furthermore, a method of cultivating cells in a cylindrical bioreactorvessel is provided. Said method comprises the steps of:

-   -   loading a flexible bioprocess bag in a cylindrical bioreactor        vessel according to the method as described above;    -   providing a cell culture medium to an inner volume of said        flexible bioprocess bag;    -   providing cells to the inner volume of said flexible bioprocess        bag;    -   cultivating the cells in the inner volume under agitation.

1. A flexible bioprocess bag comprising: a number of flexible panelswhich are sealed to each other; wherein one of the number of flexiblepanels is a bottom panel, comprising a quadrilateral middle part havingtwo opposite first side edges substantially the same length as adiameter of a cylinder substantially matching a form of a side surfaceof the bag when the flexible bioprocess bag is filled and placed withina cylindrical bioreactor vessel, said bottom panel further comprisingtwo triangular parts, each connected along their bases to one of thefirst side edges of the middle part, wherein the two first side edges ofthe middle part where the bases of the triangular parts are connectedare shorter than two remaining side edges, called second side edges ofthe middle part, wherein the two second side edges are curved such thata circle having the same diameter as a cylinder substantially matchingthe form of the side surface of the bag when the bag is filled andplaced within the cylindrical bioreactor vessel still fits inside themiddle part, and when the flexible bioprocess bag is filled said bottompanel will constitute the bottom of the bag and parts of the sidesurface of the bag, said parts of the side surface being bent side partsof the bottom panel.
 2. The flexible bioprocess bag according to claim1, wherein said bent side parts of the bottom panel are two essentiallytriangular parts.
 3. The flexible bioprocess bag according to claim 2,wherein the tops of the triangular parts point away from each other. 4.The flexible bioprocess bag according to claim 2, wherein an angle ofthe tops of the triangular parts is within the range of 75-105 degrees.5. The flexible bioprocess bag according to claim 2, wherein an angle ofthe tops of the triangular parts is within the range of 85-95 degrees.6. The flexible bioprocess bag according to claim 1, wherein the numberof flexible panels further comprises two side panels sealed to eachother along side edges, and wherein two side panels are sealed to thebottom panel to form an cylindrical side surface together with the bentside parts of the bottom panel when the bag is filled.
 7. The flexiblebioprocess bag according to claim 1, wherein the number of flexiblepanels further comprises one single side panel having two side edgeswhich are sealed to each other, and wherein said single side panel isalso sealed to the bottom panel to form a cylindrical side surfacetogether with the bent side parts of the bottom panel.
 8. The flexiblebioprocess bag according to claim 1, wherein the number of flexiblepanels further comprises a top panel, said number of flexible panelsbeing sealed to each other such that a closed bag of essentiallycylindrical form is achieved when the flexible bioprocess bag is filledand placed within the cylindrical bioreactor vessel.
 9. The flexiblebioprocess bag according to claim 1, wherein at least one connector isprovided to any one of the number of flexible panels for the purpose ofexchanging fluid from an external space to an internal space of theflexible bioprocess bag.
 10. The flexible bioprocess bag according toclaim 1, wherein at least one impeller is provided to any one of thenumber of flexible panels.
 11. The flexible bioprocess bag according toclaim 10, wherein the impeller is provided to the bottom panel.
 12. Theflexible bioprocess bag according to claim 1, wherein at least onesensor is provided to any one of the number of flexible panels.
 13. Theflexible bioprocess bag according to claim 1, wherein the flexiblebioprocess bag has an internal volume when filled of at least 10 L. 14.The flexible bioprocess bag according to claim 1, wherein the flexiblebioprocess bag is presterilized.
 15. The flexible bioprocess bagaccording to claim 1, wherein said flexible bioprocess bag is a linerfor the cylindrical bioreactor vessel or a mixer.
 16. A cylindricalbioreactor or mixer comprising the flexible bioprocess bag of claim 1.17. A method of loading a flexible bioprocess bag in a cylindricalbioreactor or mixer, comprising the steps of: providing a cylindricalbioreactor or mixer vessel; providing the flexible bioprocess bag ofclaim 21; loading said flexible bioprocess bag in said cylindricalbioreactor or mixer vessel.
 18. A method of cultivating cells in acylindrical bioreactor vessel, comprising the steps of: loading aflexible bioprocess bag in a cylindrical bioreactor vessel according tothe method of claim 17; providing a cell culture medium to an innervolume of said flexible bioprocess bag; providing cells to the innervolume of said flexible bioprocess bag; cultivating the cells in theinner volume under agitation.